Spiropyran‐Based Nanocarrier: A New Zn2+‐Responsive Delivery System with Real‐Time Intracellular Sensing Capabilities. Issue 3 (13th December 2018)

• Record Type: Journal Article
• Authors: Heng, Sabrina; Zhang, Xiaozhou; Pei, Jinxin; Adwal, Alaknanda; Reineck, Philipp; Gibson, Brant C.; Hutchinson, Mark R.; Abell, Andrew D.
• Is Part Of: Chemistry. Volume 25:Issue 3(2019)
• Page Start: 854
• Page End: 862
• Publication Date: 2018-12-13
• Subjects: apoptosis -- fluorescence -- metal ions -- payload delivery -- spiropyran-based nanocarrier; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201804816
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A new spiropyran‐based stimuli‐responsive delivery system is fabricated. It encapsulates and then releases an extraneous compound in response to elevated levels of Zn 2+, a critical factor in cell apoptosis. A C12 ‐alkyl substituent on the spiropyran promotes self‐assembly into a micelle‐like nanocarrier in aqueous media, with nanoprecipitation and encapsulation of added payload. Zn 2+ binding occurs to an appended bis(2‐pyridylmethyl)amine group at biologically relevant micromolar concentration. This leads to switching of the spiropyran (SP) isomer to the strongly fluorescent ring opened merocyanine‐Zn 2+ (MC‐Zn 2+ ) complex, with associated expansion of the nanocarriers to release the encapsulated payload. Payload release is demonstrated in solution and in HEK293 cells by encapsulation of a blue fluorophore, 7‐hydroxycoumarin, and monitoring its release using fluorescence spectroscopy and microscopy. Furthermore, the use of the nanocarriers to deliver a caspase inhibitor, Azure B, into apoptotic cells in response to an elevated Zn 2+ concentration is demonstrated. This then inhibits intracellular caspase activity, as evidenced by confocal microscopy and in real‐time by time‐lapsed microscopy. Finally, the nanocarriers are shown to release an encapsulated proteasome inhibitor (5 ) in Zn 2+ ‐treated breast carcinoma cell line models. This then inhibits intracellular proteasome and induces cytotoxicity to the carcinoma cells. Abstract : The first account of a Zn 2+ ‐responsive delivery tool with added sensing and imaging capabilities is presented. The delivery system consists of a spiropyran with an appended hydrophobic tail to allow self‐assembly into a micelle‐like structure that is shown to encapsulate payloads, for example, fluorophores and protease inhibitors, and release them in response to increased intracellular Zn 2+ levels.